2-Methoxyestradiol (2ME2), a natural metabolite of estradiol which has no estrogenic activity, is a potent antitumor and anti-angiogenic compound, currently undergoing clinical trials for treatment of a variety of cancers. In the last two decades, an ever increasing number of synthetic 2-methoxyestradiol analogues have been reported. Structural changes include A/B/C/D-rings modification, homologation, aromatization, and introduction of various substituents on C-2 position along with substitution of alkyl and ethynyl groups for the 17-hydroxy function. In this review, an attempt has been made to compile the structure-activity relationships of various synthesized 2-methoxyestradiol analogues.